Koraka Penelopie, Benton Sabrina, van Amerongen Geert, Stittelaar Koert J, Osterhaus Albert D M E
Department of Virology, Erasmus MC, Dr. Molewaterplein 50, 3015GE Rotterdam, The Netherlands.
Vaccine. 2007 Jul 20;25(29):5409-16. doi: 10.1016/j.vaccine.2007.04.079. Epub 2007 May 21.
The development of a safe and effective vaccine against dengue is a public health priority. Attempts to evaluate candidate vaccine formulations in human volunteers were largely unsuccessful, at least in part due to too high reactogenicity of some of the candidate vaccines tested. We evaluated a live attenuated tetravalent dengue vaccine candidate in flavivirus naïve and dengue virus type 3 immune non-human primates. Immune responses were measured both at the humoral and the cellular level and the efficacy of this vaccine candidate was evaluated by challenging the vaccinated animals with dengue virus type 4. Humoral and cellular immune responses upon vaccination were similar to those described after natural infection in humans. All animals were protected from developing viremia upon challenge infection. In addition, primary dengue virus type 3 infection of macaques neither influenced the immune response upon vaccination, nor interfered with vaccine-induced protection from dengue virus type 4 challenge infection. The data suggest that the live attenuated tetravalent vaccine candidate used is promising and warrant further safety and efficacy testing in clinical trials.
研发一种安全有效的登革热疫苗是公共卫生的优先事项。在人类志愿者中评估候选疫苗配方的尝试大多未成功，至少部分原因是一些受试候选疫苗的反应原性过高。我们在未感染黄病毒且对登革热病毒3型免疫的非人灵长类动物中评估了一种减毒活四价登革热候选疫苗。在体液和细胞水平上测量免疫反应，并通过用登革热病毒4型攻击接种疫苗的动物来评估该候选疫苗的效力。接种疫苗后的体液和细胞免疫反应与人类自然感染后描述的反应相似。所有动物在受到攻击感染后均受到保护，未出现病毒血症。此外，猕猴初次感染登革热病毒3型既不影响接种疫苗后的免疫反应，也不干扰疫苗诱导的对登革热病毒4型攻击感染的保护作用。数据表明，所使用的减毒活四价候选疫苗很有前景，值得在临床试验中进一步进行安全性和有效性测试。
